Although liver fatty acid-binding protein (L-FABP) is an important binding site for various hydrophobic ligands in hepatocytes, its vivo significance not understood. We have therefore created L-FABP null mice and report here their initial analysis, focusing on the impact of this mutation hepatic acid capacity, lipid composition, expression other lipid-binding proteins. Gel-filtered cytosol from lacked main peak fraction that normally comprises both sterol carrier protein-2 (SCP-2). The...

Endocannabinoids (ECs) and cannabinoids are very lipophilic molecules requiring the presence of cytosolic binding proteins that chaperone these to intracellular targets. While three different fatty acid (FABP3, -5, -7) serve this function in brain, relatively little is known about how such hydrophobic ECs transported within liver. The most prominent hepatic FABP, liver protein (FABP1 or L-FABP), has high affinity for arachidonic (ARA) ARA-CoA, suggesting FABP1 may also bind ARA-derived (AEA...

Although liver fatty acid binding protein (L-FABP) is postulated to influence cholesterol homeostasis, the physiological significance of this hypothesis remains be resolved. This issue was addressed by examining response young (7 wk) female mice L-FABP gene ablation and a cholesterol-rich diet. In control-fed mice, alone induced hepatic accumulation (2.6-fold), increased bile levels, body weight gain (primarily as fat tissue mass). cholesterol-fed further enhanced (especially ester, 12-fold)...

Although the function of liver fatty acid binding protein in hepatic metabolism has been extensively studied, its potential role cholesterol homeostasis is less clear. accumulation was initially reported L-FABP-null female mice, that study performed with early N2 backcross generation mice. To resolve whether phenotype these L-FABP −/− mice attributable to genetic inhomogeneity, were further backcrossed C57Bl/6 up N10 (99.9% homogeneity) generation. Hepatic total observed female, but not...

Although the physiological roles of individual bile acid synthetic enzymes have been extensively examined, relatively little is known regarding function intracellular acid-binding proteins. Male L-FABP (liver fatty-acid-binding protein) gene-ablated mice were used to determine a role for L-FABP, major liver protein, in and biliary cholesterol metabolism. First, control-fed gene ablation alone increased total pool size by 1.5-fold, especially gall-bladder liver, but without altering...

Although liver fatty acid binding protein (L-FABP) is known to bind not only long chain (LCFA) but also acyl CoA (LCFA-CoA), the physiological significance of LCFA-CoA has been questioned and remains be resolved. To address this issue, effect L-FABP gene ablation on cytosolic binding, pool size, esterification, potential compensation by other intracellular proteins was examined. resulted in loss concomitant upregulation two proteins, (ACBP) sterol carrier protein-2 (SCP-2), 45 80%,...

Liver fatty acid binding protein (L-FABP) is the major soluble that binds very-long-chain n-3 polyunsaturated acids (n-3 PUFAs) in hepatocytes. However, nothing known about L-FABP's role PUFA-mediated peroxisome proliferator activated receptor-α (PPARα) transcription of proteins involved long-chain (LCFA) β-oxidation. This issue was addressed cultured primary hepatocytes from wild-type, L-FABP-null, and PPARα-null mice with these findings: 1) increase expression PPARα-regulated LCFA...

Although the human liver fatty acid binding protein (L-FABP) T94A variant arises from most commonly occurring single-nucleotide polymorphism in entire FABP family, there is a complete lack of understanding regarding role this disease. It has been hypothesized that substitution results loss ligand ability and function analogous to seen with L-FABP gene ablation. This possibility was addressed using recombinant wild-type (WT) T94T cultured primary hepatocytes. Nonconservative replacement...

The human liver fatty acid-binding protein (L-FABP) T94A variant, the most common in FABP family, has been associated with elevated triglyceride levels. How this amino acid substitution elicits these effects is not known. This issue was addressed using recombinant wild-type (WT) and variant L-FABP proteins as well cultured primary hepatocytes expressing respective (genotyped TT, TC CC). did alter or only slightly altered binding affinities for saturated, monounsaturated polyunsaturated long...

The liver expresses high levels of two proteins with affinity for long-chain fatty acids (LCFAs): acid binding protein (L-FABP) and sterol carrier protein-2 (SCP-2). Real-time confocal microscopy cultured primary hepatocytes from gene-ablated (L-FABP, SCP-2/SCP-x, L-FABP/SCP-2/SCP-x null) mice showed that the loss L-FABP reduced cellular uptake 12- N-methyl-(7-nitrobenz-2-oxa-1,3-diazo)-aminostearic (a fluorescent-saturated LCFA analog) by ∼50%. Importantly, nuclear targeting was enhanced...

A major gap in our knowledge of rapid hepatic HDL cholesterol clearance is the role key intracellular factors that influence this process. Although reverse transport pathway targets to liver for net elimination free from body, molecular details governing uptake into hepatocytes are not completely understood. Therefore, effects sterol carrier protein (SCP)-2 and fatty acid-binding (L-FABP), high-affinity cholesterol-binding proteins present hepatocyte cytosol, on HDL-mediated were examined...

While TOFA (acetyl CoA carboxylase inhibitor) and C75 (fatty acid synthase prevent lipid accumulation by inhibiting fatty synthesis, the mechanism of action is not simply accounted for inhibition enzymes alone. Liver binding protein (L-FABP), a mediator long chain signaling to peroxisome proliferator-activated receptor- α (PPAR ) in nucleus, was found bind its activated thioester, TOFyl-CoA, with high affinity while C75-CoA lower affinity. Binding significantly altered L-FABP secondary...

While a high-cholesterol diet induces hepatic steatosis, the role of intracellular sterol carrier protein-2/sterol protein-x (SCP-2/SCP-x) proteins is unknown. We hypothesized that ablating SCP-2/SCP-x [double knockout (DKO)] would impact lipids (cholesterol and cholesteryl ester), especially in high-cholesterol-fed mice. DKO did not alter food consumption, body weight (BW) gain decreased females, concomitant with steatosis females less so males. DKO-induced control-fed wild-type (WT) mice...

Liver fatty acid-binding protein (FABP1, L-FABP) has high affinity for and enhances uptake of arachidonic acid (ARA, C20:4, n-6) which, when esterified to phospholipids, is the requisite precursor synthesis endocannabinoids (EC) such as arachidonoylethanolamide (AEA) 2-arachidonoylglycerol (2-AG). The brain derives most its ARA from plasma, taking up transporting it intracellularly via cytosolic proteins (FABPs 3,5, 7) localized within brain. In contrast, much more prevalent FABP1 not...

The endocannabinoid system shifts energy balance toward storage and fat accumulation, especially in the context of diet-induced obesity. Relatively little is known about factors outside central nervous that may mediate effect high-fat diet (HFD) on brain levels. One candidate liver fatty acid binding protein (FABP1), a cytosolic highly prevalent liver, but not detected brain, which facilitates hepatic clearance acids. impact Fabp1 gene ablation (LKO) plasma levels was examined data expressed...

Although sterol carrier protein-2 (SCP-2) is encoded as a precursor protein (proSCP-2), little known regarding the structure and function of 20-amino acid N-terminal presequence. As shown herein, presequence contains significant secondary alters SCP-2: (i) (CD), (ii) tertiary (aqueous exposure Trp by UV absorbance, fluorescence, fluorescence quenching), (iii) ligand binding site [Trp response to ligands, peptide cross-linked photoactivatable free cholesterol (FCBP)], (iv) selectivity for...

Although HDL-mediated cholesterol transport to the liver is well studied, efflux from hepatocytes back HDL less understood. Real-time imaging of 22-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-amino)-23,24-bisnor-5-cholen-3beta-ol (NBD-cholesterol), which poorly esterified, and [(3)H]cholesterol, extensively cultured primary wild-type sterol carrier protein-2 (SCP-2) gene-ablated mice showed that 1) NBD-cholesterol was affected by type lipoprotein acceptor, i.e., HDL3 over HDL2; 2) rapid (detected...